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      Common and unique features of viral RNA-dependent polymerases

      review-article
      Author(s):
      Publication date (Electronic):
      Journal: Cellular and Molecular Life Sciences
      Publisher: Springer Basel
      Keywords: RNA virus, Retrovirus, RdRp, Reverse transcriptase, Dynamics

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          Abstract

          Eukaryotes and bacteria can be infected with a wide variety of RNA viruses. On average, these pathogens share little sequence similarity and use different replication and transcription strategies. Nevertheless, the members of nearly all RNA virus families depend on the activity of a virally encoded RNA-dependent polymerase for the condensation of nucleotide triphosphates. This review provides an overview of our current understanding of the viral RNA-dependent polymerase structure and the biochemistry and biophysics that is involved in replicating and transcribing the genetic material of RNA viruses.

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          Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus

          Abdullah Assiri, Allison McGeer, Trish M. Perl … (2013)
          In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.
          Article 0 comments Cited 718 times – based on 0 reviews     Review now
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            Global Spread and Persistence of Dengue

            Jennifer L. Kyle, Eva Harris (2008)
            Dengue is a spectrum of disease caused by four serotypes of the most prevalent arthropod-borne virus affecting humans today, and its incidence has increased dramatically in the past 50 years. Due in part to population growth and uncontrolled urbanization in tropical and subtropical countries, breeding sites for the mosquitoes that transmit dengue virus have proliferated, and successful vector control has proven problematic. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have expanded from South and Southeast Asia into the Pacific and the Americas. This review explores the human, mosquito, and viral factors that contribute to the global spread and persistence of dengue, as well as the interaction between the three spheres, in the context of ecological and climate changes. What is known, as well as gaps in knowledge, is emphasized in light of future prospects for control and prevention of this pandemic disease.
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              The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit.

              Alexandre Dias, Denis Bouvier, Thibaut Crépin … (2009)
              The influenza virus polymerase, a heterotrimer composed of three subunits, PA, PB1 and PB2, is responsible for replication and transcription of the eight separate segments of the viral RNA genome in the nuclei of infected cells. The polymerase synthesizes viral messenger RNAs using short capped primers derived from cellular transcripts by a unique 'cap-snatching' mechanism. The PB2 subunit binds the 5' cap of host pre-mRNAs, which are subsequently cleaved after 10-13 nucleotides by the viral endonuclease, hitherto thought to reside in the PB2 (ref. 5) or PB1 (ref. 2) subunits. Here we describe biochemical and structural studies showing that the amino-terminal 209 residues of the PA subunit contain the endonuclease active site. We show that this domain has intrinsic RNA and DNA endonuclease activity that is strongly activated by manganese ions, matching observations reported for the endonuclease activity of the intact trimeric polymerase. Furthermore, this activity is inhibited by 2,4-dioxo-4-phenylbutanoic acid, a known inhibitor of the influenza endonuclease. The crystal structure of the domain reveals a structural core closely resembling resolvases and type II restriction endonucleases. The active site comprises a histidine and a cluster of three acidic residues, conserved in all influenza viruses, which bind two manganese ions in a configuration similar to other two-metal-dependent endonucleases. Two active site residues have previously been shown to specifically eliminate the polymerase endonuclease activity when mutated. These results will facilitate the optimisation of endonuclease inhibitors as potential new anti-influenza drugs.
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                Author and article information

                Contributors
                Aartjan J. W. te Velthuis: +44 0 1865275579 , aartjan.tevelthuis@path.ox.ac.uk
                Journal
                Journal ID (nlm-ta): Cell Mol Life Sci
                Journal ID (iso-abbrev): Cell. Mol. Life Sci
                Title: Cellular and Molecular Life Sciences
                Publisher: Springer Basel (Basel )
                ISSN (Print): 1420-682X
                ISSN (Electronic): 1420-9071
                Publication date (Electronic): 1 August 2014
                Publication date PMC-release: 1 August 2014
                Publication date (Print): 2014
                Volume: 71
                Issue: 22
                Pages: 4403-4420
                Affiliations
                [ ]Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
                [ ]Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE UK
                Article
                Publisher ID: 1695
                DOI: 10.1007/s00018-014-1695-z
                PMC ID: 4207942
                PubMed ID: 25080879
                SO-VID: d825167c-e573-4327-88d0-7f6bacb2e70a
                Copyright © © The Author(s) 2014
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                Date received : 10 April 2014
                Date revision received : 29 June 2014
                Date accepted : 28 July 2014
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © Springer Basel 2014

                ScienceOpen disciplines: Molecular biology
                Keywords: rna virus,retrovirus,rdrp,reverse transcriptase,dynamics
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: rna virus, retrovirus, rdrp, reverse transcriptase, dynamics

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